A variety of contraception methods are currently available; some require significant user involvement. While the effectiveness of existing contraceptives, including barrier methods and hormonal therapies, is well established, overcoming user non-compliance to improve overall efficacy has proven difficult.
A widely used contraception method that is less susceptible to user non-compliance are intrauterine devices (IUDs). IUDs have been found to have higher rates of reliability and are effective for a longer period of time than most other commercially available contraceptives. Additionally, the efficacy of IUDs made of copper or having copper as an active agent appear to be higher than non-metallic IUDs, and are effective for even longer periods of time (e.g. approximately 10 years). This type of IUD releases copper ions when in contact with intrauterine fluid and creates a hostile environment for conception. However, copper IUDs are associated with an increase in bleeding and cramping during the initial period of use. This initial release of copper ions is referred to as “burst release”. Following the first few months of copper IUD implantation, users will experience normal cycles with the contraceptive advantages. Further, copper IUDs are also associated with severe corrosion and fragmentation of the copper in the IUD, as early as the first year of use. This copper fragmentation occurs even in commercially available IUDs having a support structure made of biocompatible, non-degradable material where a copper wire is wound around the support structure; the copper wire corrodes and breaks apart. Copper fragmentation may cause subsequent expulsion of fragmented parts of the IUD, increasing the risk of undesirable pregnancies, and reducing the effective period of use of the IUD.
Traditionally some copper IUDs are made with a wire of biocompatible, non-degradable materials having a thin coating of copper (U.S. Pat. No. 4,351,326). While this type of IUDs minimizes fragmentation by maintaining the structural integrity of the wire, the undesirable burst release of copper ions during the initial period after implantation may still occur. Further, the thin copper coating of the wire may substantially reduce the effective contraceptive period of the IUDs. More recently, some IUDs may include a copper alloy wire having a combination of metallic materials to increase the release of copper ions for a given surface area of copper, reduce bleeding and reduce infections after implantation (U.S. Pat. No. 8,118,028). However, the copper alloy wire having metals that increase the galvanic reaction of copper may accelerate its degradation and corrosion, therefore, reducing the effective period of use of the IUD. Additionally, the copper alloy may still be subject to undesirable fragmentation. Other IUDs may include a copper wire coated with a thin layer of degradable and bioabsorbable polymeric material to minimize the burst release of copper ions (WO 2012/063262). However, the polymeric layer degrades and is absorbed within the first few months of IUD implantation leaving the copper wire subject to corrosion and fragmentation that may reduce the effective period of use.
Therefore, there is an ongoing need to provide for more suitable copper IUDs that control the release rate of copper ions, particularly, during the initial period after implantation in a uterus, minimizing the undesirable side effects of the burst release of copper ions while maintaining the structural integrity and extending the contraceptive effective period of use of the IUD.